PROJECTSUMMARY Anxietydisorders,asagroup,arethemostcommonmentalillnessesintheUS,affectingabout25%ofado- lescentsand18%ofadults.Symptomstypicallybegininchildhoodoradolescence.Acrucialgapinstudiesof anxietyisthelackofempiricaldatalinkingpediatricanxietytoabnormalbraindevelopment.Thisfour-yearK01 applicationpresentsaprogramforresearchandtrainingthatwillsupporttheapplicantonapathtowards becominganNIH-fundedindependentinvestigator,focusedonstudyingtheneuralcorrelatesoffeargenerali- zationinyouthwithpathologicalanxietyusinginterdisciplinaryapproaches(affectiveneuroscience,multimodal neuroimaging,andcomputationalmethods).Thetrainingplanbuildsonthecandidate?sprevioustrainingand experience,andcapitalizesonamentorshipteamandaresearchenvironmenttofosterdevelopmentofthe candidate?sexpertisein(1)thephenomenologyofanxietydisorders;?(2)patient-oriented,translationaland developmentalneuroscienceofanxiety;?(3)advancedcomputationalneuroimaging;?and(4)responsibleand ethicalconductinscientificresearchinvulnerableindividuals.Theresearchprojectwillinvestigatefeargener- alizationbehavioranditsrelationshipwithvmPFC(ventromedialprefrontalcortex)functionandcorticolimbic connectivityinhealthyyouth(Aim#1),andinvestigatefearover-generalizationbehavioranditsrelationship withvmPFCfunctionandcorticolimbicconnectivityinyouthwithpathologicalanxiety(Aim#2).Wehypothesize thatchildhoodanxietyinvolvesfearover-generalizationandthatfearover-generalizationinvolvesabnormal functionandconnectivityofthecorticolimbicsystem.Totestthesehypotheses,wewilluseafeargeneraliza- tionfMRItaskandmultimodalMRI(structural,diffusion,andfunctionalMRI)inhealthyyouthwithoutanxiety (n=25)aswellasinyouthwithpathologicalanxietyacrossaspectrumofseverity(i.e.,thosewithsubthreshold anxiety[n=25]andthosewithanyDSM-5anxietydisorder[n=25]).Successfulcompletionofthisstudywill providecross-sectionalevidenceoftheassociationofpediatricanxietywithfeargeneralizationbehavior, vmPFCfunction,andcorticolimbicsystemconnectivity.Themultipleunitsofanalysiswillhelpelucidatebrain- behaviorrelationshipsunderlyingfeargeneralization.Thesedataalongwiththeresearchexpertisedeveloped throughthisK01awardwillsupportafutureR01applicationtotrackovertimethedevelopmentaltrajectoriesof feargeneralizationandpathologicalanxietyinyouth.Theultimategoalofthislineofresearchistodevelop neurobehavioralmarkerstodeterminewhenandwheretointerveneinanxietydisorders(NIMHStrategic Objective2)andtopromotepreventivetherapeuticinterventionstoyouthwithpathologicalanxiety(NIMH StrategicObjective3).